Macromolecule, bioactive

It appears that none of these process techniques is dominant, at least with the lactide/glycolide materials. Researchers have considerable choices available in regard to fabrication of microspheres from these polymers. The most commonly used procedures employ relatively mild conditions of pH and temperature and are usually quite compatible with the bioactive agents to be entrapped, including proteins and other macromolecules. Only in the case of live virus and living cell encapsulation have serious deactivation problems been encountered and those problems were due to solvents used in the process. 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

Allcock, H. R., Austin, P. E., and Neenan, T. X., Phosphazene high polymers with bioactive substituent groups Prospective anesthetic aminophosphazenes, Macromolecules. 15, 689, 1982. 

Huang J, Habraken G, Audouin F, Heise A (2010) Hydrolytically stable bioactive synthetic glycopeptide homo- and copolymers by combination of NCA polymerization and click reaction. Macromolecules 43 6050-6057... 

Most published work on the design and fabrication of nanostructures from biological macromolecules relate to DNA and proteins the use of other biopolymers, such as cyclodextrins [2], was far less developed. Because the use of DNA is intensively covered in Chapter 10 of this volume (also see Ref 3), as well as recently described by Seeman [4,5] this chapter will focus on proteins as a potential tool for the construction of nanostructures. Hence this chapter is focused on literature that may provide a basis for the identification of gnidelines, methodologies, and examples having potential for farther development of new protein-based composite nanostrnctnres integrating strnctnral and bioactive components. 

So far, the prevalent method to immobilize protein is sol-gel/polymer embedment of protein. It usually embeds and immobilizes protein in a three-dimensional netlike structure of macromolecule polymer. This technology has some characteristics such as mild conditions, multifarious sol-gels, and controllable membrane aperture and figure. It can also retain the bioactivity of protein well when applied to a high concentration of protein. However, the aggregation process is difficult to control. 

A rare but serious event that can result from irreversible CYP inhibition is the development of a hypersensitivity reaction. The bioactivation of a drug and the formation of a covalent adduct between the activated substrate and the enzyme can lead to hapten formation and eventually to an idiosyncratic autoimmune response (usually in the form of autoimmune hepatitis) [14]. The hapten formation is the first key step toward the autoimmune response. The CYP macromolecule is made immunogenic ( foreign ) by the covalent binding of the electrophilic metabolites, and the immune reaction follows with the production of autoantibodies against the target molecule (not necessarily alkylated). 

From a purely pragmatic perspective, it is clear that reactive metabolites are linked with toxicity and that a circumstantial link can be made to idiosyncratic toxicides. Consequently, even though the mechanism of this toxicity is not fully understood, since assays are available to measure the potential for bioactivation in an ideal world one would not carry this liability forward. Conversely, it is not an ideal world, all drug molecules have challenges and the definition of therapeutic index (i.e., the ratio between the toxic exposure and the therapeutic exposure) is critical. Covalent binding of reactive metabolites to macromolecules is a crude measure and not a full predictor of toxicity and it is well known that toxicity can be ameliorated by a lower dose. Furthermore, the so-called definitive assays require radiolabeled drug material which is expensive and generally slow to produce. 

From a chemical point of view, the half-life of fluorine-18 allows multi-step synthetic approaches that can be extended over hours. Fluorine-18 has therefore, in spite of its somewhat limited chemical repertoire, been effectively used for the labelling of numerous both relatively simple and complex bioactive chemical structures [3,5-9], including high-molecular-weight macromolecules such as peptides, proteins [10-13] and oligonucleotides [14-18]. General considerations on radiochemistry involving short-lived positron emitters will be discussed in Section 2.3. 

Jain et al. (33) used the microemulsion system Triton X-100/cyclo-hexane/hexanol/water/ammonia to prepare silica nanoparticles with entrapped bioactive macromolecules fluorescein isothiocyanate-dextran (FITC-Dx) (mol. mass 19.6 kD), [125I]tyraminylinulin (mol. mass 5 kD), and horseradish peroxidase (HRP) (mol. mass 40 kD). The biomolecules were first solubilized in the microemulsion, and the alkoxide (TMOS) was then added. To ensure small particle sizes, the reaction was conducted under ice-cold temperatures (in a refrigerator for 72 h). 

Mollusks along with the crustaceans are also widely sought to participate in the world s consumption of marine food. Fermented marine food sauces such as blue mussel sauce and oyster sauce possess bioactive peptides which play a major role as Angiotensin I converting enzyme inhibitors that indirectly suppress hypertension (Wijesekara and Kim, 2010). Hence, the mollusk-derived proteins and other macromolecules are highly valuable to indicate these organisms as medicinally valuable food sources. 

Bioactive macromolecules like peptides, proteins, and nucleic acids have been successfully embedded in planar LbL films. An important question is the retention of the bioactivity of the film-embedded biomolecules. The structural properties and stability of the LbL films formed from synthesized polypeptides of various amino acid sequences were recently reported [50]. The authors showed that control over the amino acid sequence enables control over non-covalent interpolypeptide interaction in the film, which determines the film properties. Haynie and coworkers showed by circular dichroism spectroscopy that the extent of adsorption of poly(L-glutamic acid) (PGA) and poly(L-lysine) (PLL) in the LbL films scales with the extent of secondary structure of the polypeptides in solution [51]. Boulmedais demonstrated that the secondary structure of the film composed of these polypeptides is the same as the peptide structure in the complex formed in solution [52], as found by Fourier transform IR spectroscopy (FUR). 

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